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Immunoglobulin A (IgA) nephropathy (IgAN) is most prevalent and likely to progress to kidney failure in individuals of East Asian ancestry, followed by individuals of White race and ethnicity. Nefecon, a novel, oral, targeted-release budesonide formulation, is specifically designed to treat IgAN by inhibiting galactose-deficient (Gd-IgA1) formation in the Peyer’s patch–rich distal ileum. Part A of the phase III NefIgArd clinical trial reported significant reductions in urine protein–creatinine ratio (UPCR) and significant benefit on estimated glomerular filtration rate (eGFR) with Nefecon versus placebo over 9 months of treatment followed by 3 months off treatment (Barratt J, et al. Kidney Int. 2023;103:391-402). The observed benefits were maintained over a further 12‑month period off treatment. Here, we analyzed the full 2-year NefIgArd data to assess responses to Nefecon treatment in patients identifying as Asian or White.
NefIgArd is a global, double-blinded, randomized, placebo-controlled trial in patients with IgAN at high risk despite optimized supportive care. Eligibility criteria included biopsy-confirmed primary IgAN, persistent proteinuria (UPCR ≥0.8 g/g or proteinuria ≥1 g/24 h), and an eGFR of 35-90 mL/min/1.73 m2. Patients received Nefecon 16 mg/day or placebo in addition to supportive care for 9 months, followed by 15-months off treatment. Weighted eGFR average over 2 years and UPCR at 9 and 24 months were stratified according to whether patients had self-reported as ‘Asian’ or ‘White’. Race and ethnicity categories were defined based on those specified by the US Food and Drug Administration (FDA).
In the full analysis set (N=364), patients identified as Asian (n=83), White (n=275), or Other (n=6). Over the entire study period, there was a significant difference between the Nefecon versus placebo arms in the ratio of geometric least-squares means for eGFR-weighted average over 2 years for Asian (p=0.0082) and White (p<0.0001) patients, with the estimated absolute change in eGFR favoring Nefecon versus placebo by 5.5 mL/min/1.73 m2 in Asian patients and 4.8 mL/min/1.73 m2 in White patients (Table 1). There was a greater estimated reduction in UPCR in the Nefecon versus placebo arms at 9 and 24 months, irrespective of race and ethnicity (Asian patients: 23.4% and 26.7%, respectively; White patients: 32.0% and 32.1%, respectively [Table 2]). Notably, the time to a confirmed 30% reduction in eGFR or kidney failure event was significantly delayed with Nefecon versus placebo irrespective of race or ethnicity [Asian patients: hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.09, 0.91 [p=0.0239 {one-sided}]; White patients: HR 0.48, 95% CI 0.28, 0.83 [p=0.0046 {one-sided}]). In addition, Nefecon significantly reduced the rate of microhematuria, irrespective of race and ethnicity (odds ratio vs placebo in: Asian patients, 3.5 [p=0.0303]; White patients, 2.3 [p=0.0030]). Nefecon was also well tolerated, with a safety profile as expected for a locally acting oral budesonide product.
These findings indicate that Nefecon was efficacious and well tolerated irrespective of White or Asian race and ethnicity.